The ultimate objective of the proposed studies is to demonstrate the unique usefulness of the applicants' strategy for HIV vaccine discovery which has three basic components: (i) an impartial screen for protective antigens that is conducted systematically; (ii) the use of partial rather than complete pathogen-gene products as genetic antigens; and (iii) exploitation of antigen presenting cells to optimize immune-reactivity. The screening procedure, termed ELI sibbing, was developed by the investigators and successfully applied to several bacterial genomes. The applicants plan to produce an HIV genetic library that encodes the entire viral genome and that expresses antigens as short (100 to 200 amino acid) sub-proteins in an inoculated animal. This effort has been already initiated. The applicants also intend to use the rapid and methodical ELI procedure to screen the immune responses elicited by sub-grouped library components. The identification of individual immune responsive library members should be accomplished. Finally, the applicants propose to maximize the effectiveness of antigen presenting cells by defining conditions that influence their immune activities and targeting genetic vaccines, in situ, to this small population of important cells.